Malaria Drugs (Ceryak)

Question 1

Name artemisinins (2)

Answer 1

• artemether

- artesunate

Question 2

Quinolines (3)

Answer 2

• chloroquine phosphate
• quinine sulfate/quinidine gluconate
• primaquine

Question 3

Adjunctive with quinolines (2)

Answer 3

• doxycycline

- clindamycin

Question 4

Artemisinins target species

Answer 4

P. falciparum and P. vivax

Question 5

How do artemisinins function as anti-malaria

Answer 5

endoperoxide moeity (free radial production)

Question 6

Artemisinins resistance due to

Answer 6

counterfeit drugs

Question 7

Which artemisinin is given orally and which is IV/rectal?

Answer 7

Oral: artemether

IV/Rectal” artesunate

Question 8

How are artemisinins absorbed, metabolized, and excreted

Answer 8

Rapid absorptions, metabolism (CYP), biliary excretion

Question 9

Describe the artemisinin half life; prophylaxis?

Answer 9

Short! (1-2 hours); not useful for prophylaxis; not good as monotherapy

Question 10

Artemisinin-based combo therapues (ACTs)

Answer 10

increase efficacy and decrease resistance

Question 11

Artemisinin adverse effects

Answer 11

• generally well-tolerated, not recommended for children <5kg or during 1st trimester of pregnancy
• reduced RBC and neutrophils; transient heart block (rare, dose-related, reversible)

Question 12

Coartem =

Answer 12

artemether and lumefantrine; which both target blood stages

Question 13

What is beneficial about coartem?

Answer 13

large Vd and 4-5 day half-life

Question 14

Coartem problem

Answer 14

substantial drug-drug interaction with antiretrovirals/protease inhibitors (may need to increase dose)

Question 15

How should pts take ACTs?

Answer 15

with fatty food or whole milk (if pt vomits within 30 min, repeat dose)

Question 16

What pts are ACTs contraindicated in?

Answer 16

Cardiac arrhythmias, cardiac disease

Question 17

How do you get artesunate?

Answer 17

CDC!

Question 18

Quinolines and related compounds mechansim

Answer 18

interfere with heme digestion

Question 19

Chloroquine mechanism of action

Answer 19

• plasmodium digest host cell hemoglobin
• process releases large amts of heme, which is toxic to plasmodium
• normally, plasmodium polymerizes heme to nontoxic hemozoin
• chloroquine prevents polymerization to hemozoin

Question 20

Chloroquine resistance

Answer 20

pfcrt mutation - increased drug efflux

Question 21

Is chloroquine safe in pregnancy?

Answer 21

Yes!

Question 22

Oral chloroquine adverse effects

Answer 22

• Visual disturbances
• pruritis in African descent
• rare hemolysis w/ pt w/ G6PD deficiency
• discoloration of nail beds/mucous membranes

Question 23

Chloroquine parental doses > 5g

Answer 23

usually fatal!

-CV and CNS (irreversible retinopathy, arrhythmias, etc.)

Question 24

What pt is chloroquine contraindicated in?

Answer 24

• pt w/ epilepsy/myasthenia gravis bc affects neuro-muscular transmission
• pt w/ psoriasis/porphyria cutanea tarda

Question 25

Chloroquine caution in pt w/...

Answer 25

- pt w/ advanced liver or GI disease, neurological or blood disorders (G6PD deficiency) - pt w/ cardiac dysarhythmias

Question 26

What to avoid while taking chloroquine

Answer 26

- kaolin (clay mineral) and Ca2+/Mg2+ containing antacids (delay GI absorption) - concomitant administration of cimetidine (inhibits metabolism of chloroquine)

Question 27

Quinine use against...

Answer 27

chloroquine-R and MDR P. falciparum asexual blood stages, gametocyticidal against P. vivax and P.ovale

Question 28

Quinine mechanism

Answer 28

interferes w/ heme digestion

Question 29

What is different about IV quinine?

Answer 29

more potent/toxic

Question 30

Quinine absorption, metabolism, excretion

Answer 30

Readily absorbed (good tissue distribution in CNS and placenta); hepatic metabolism CYP3A4; renal excretion

Question 31

Quinine resistance

Answer 31

Pfmdr1 gene amplification (pumps out drug)

Question 32

Quinine adverse effects (dose-related toxicities)

Answer 32

-cinchonism = tinnitus, deafness, visual disturbance, headache, nausea, vomiting, dizziness, postural hypotension (reversible)

Question 33

Quinine adverse effects (hypersensitivity)

Answer 33

rash, urticaria, angioedema, bronchospams | -blackwater fever: severe hemolysis; hemoglobinemia

Question 34

When do you stop quinine treatment?

Answer 34

Hemoglobinuria

Question 35

Increased hemolysis with quinines in pt w/...

Answer 35

G6PD deficiency

Question 36

Quinine contraindicated in pt w/...

Answer 36

pt w/ tinnitus/optic neurititis

Question 37

Quinine caution in pt w/...

Answer 37

- pt w/ hypersensitivity (discontinue if evidence of hemolysis) - pt w/ cardiac dysrhythmias - pregnancy (possibly safe) - decrease dose w/ renal insufficiency - aluminum/magnesium-containing antacids delay GI absorption - CYP3A4 inhibition